With rapid progress or development of leading-edge research on biotechnology including genomic drug discovery and genetic diagnosis or therapy, nucleic acid oligomers such as DNA probes, siRNA, antisense DNA, and antisense RNA have been actively utilized in recent years. Solid-phase synthesis methods using phosphoramidite are typically known as methods for synthesizing these nucleic acid oligomers.
Patent Literature 1 has proposed a method for synthesizing a nucleic acid oligomer in a liquid phase, wherein a nucleoside compound in which polyethylene glycol (PEG) as a hydrophilic polymer having a molecular weight distribution is introduced in the base moiety of a nucleoside is used as an end starting material or a building block to facilitate separating or purifying an intermediate product, thereby synthesizing a nucleic acid oligomer. Non Patent Literature 1 has proposed a method for producing a nucleic acid oligomer by: synthesizing nucleotide dimers or trimers in which adenine as the base moiety of a nucleoside is substituted by an unsubstituted benzoyl group by repeating reaction in a liquid phase and column chromatography purification; and binding these dimers or trimers by a phosphoramidite method, followed by column chromatography purification. Alternatively, Non Patent Literature 2 has proposed a method for producing a nucleic acid oligomer by: subjecting a nucleoside in which thymine as the base moiety of a nucleoside is substituted by a p-methoxybenzoyl group (p-toluyl group) to a phosphoric acid triester method in a liquid phase; and performing column chromatography purification after every reaction.
Meanwhile, Patent Literature 2 has proposed the easy step of separating by-products, etc. after reaction using, as an organic synthesis reagent, a compound having the property of shifting its liquid-phase state to a solid-phase state depending on change in solution composition or solution temperature after organic synthesis reaction. The literature has further described, as such an organic synthesis reagent, a compound having a group retaining hydrophobicity on an aromatic ring, for example, a benzylamine substituted by two docosyloxy groups as alkoxy groups each having 22 carbon atoms, and proposed use thereof for peptide synthesis.